NKG2D+ IFN-γ+ CD8+ T Cells Are Responsible for Palladium Allergy

Abstract

Nickel, cobalt, and chromium are well known to be causal agents of allergic contact dermatitis. Palladium (Pd) can also cause allergic disease and exposure results from wide use of this metal in dental restorations and jewelry. Metal allergy is categorized as a delayed-type hypersensitivity, and metal-responsive T cell clones have been isolated from allergic patients. However, compared to nickel, little is known about the pathology of allergic disease mediated by Pd, and pathogenic T cells are poorly understood. To identify the pathogenic T cells that are responsible for onset of Pd allergy, we enriched metal-responsive lymphocytes by sequential adoptive transfer of involved lymph node cells. Here we show that sequential adoptive transfer gradually increased the incidence and the intensity of Pd allergy, and CD8+ T cells are responsible for the disease as CD8+ T cell-depleted mice and β2-microglobulin-deficient mice did not develop Pd allergy. In addition, we found that draining lymph node cells skewed toward CD8+ T cells in response to Pd challenge in 8th adoptive transferred recipient mice. The CD8+ T cells expressed NKG2D, a costimulatory molecule involved in the production of IFN-γ. NKG2D ligand was also induced in Pd-injected tissues. Furthermore, both NKG2D ligand-transgenic mice, where NKG2D is downmodulated, and IFN-γ-deficient mice showed impaired Pd allergy. Taken together, these results indicate that IFN-γ-producing NKG2D+ CD8+ T cells are responsible for Pd allergy and suggest that NKG2D is a potential therapeutic target for treatment of metal allergy.

Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals

“…Massive expansion of CD8 + TCs in response to antigens has already been described in another study . In agreement with our results, the activation of the CD8 + TC population triggered by AHCP had previously been related to metal allergy and hapten‐induced contact hypersensitivity …”

“…38 In agreement with our results, the activation of the CD8 + TC population triggered by AHCP had previously been related to metal allergy and hapteninduced contact hypersensitivity. [39][40][41] The CD124 marker was selected as the most relevant for assessing TC activation in this model, as it showed the highest increases with AHCP and LPS as compared with HBSS. CD124 membrane marker expression has already been described in the Th2-type immune response, 33,42,43 and AHCP has been reported to induce a Th2-type immune response after in vivo exposure.…”

TRAV7-2*02 Expressing CD8+ T Cells Are Responsible for Palladium Allergy

“…Therefore, we used PdCl 2 for these experiments and referred the appropriate dose of PdCl 2 [6,15,16]. Interestingly, since Na 2 [PdCl 4 ] has been shown to be effective in human patch testing [17], Na 2 [PdCl 4 ] may be more useful reagent than PdCl 2 in Pd allergic mouse model.…”

Role of interleukin-18 in the pathophysiology of allergic diseases

“…CD8+ T cells have paradoxical effects, as they have been reported to be the mediators of palladium and amoxicillin allergies, while also able to non-specifically inhibit allergic sensitization and promote a Th1 response during a Th2 allergic response. In both examples of drug allergy, CD8+ cells were enriched upon sensitization and were still able to effect an allergic response after adoptive transfer to naïve mice, and CD8+-derived IFN-γ was implicated as a key mediator [73,74]. In the studies demonstrating an inhibition of allergic sensitization, memory CD8+ cells stimulated DCs to promote Th1 cells, but in this response the IFN-γ derived from Th1 cells [75,76].…”